Small Creature, Massive Genome
The Mexican salamander offers insights into regeneration
The Mexican salamander, or the axolotl, may have tiny feet, but the feat of decoding its genetic footprint was huge — 32 billion base pairs huge, making it ten times bigger than the human genome and the largest ever sequenced.
The accomplishment by an international team of scientists is significant, not only because of its sheer size, but also because of the insights it could provide into tissue regeneration.
The easily recognizable critter has an astounding ability to regenerate body parts, growing lost limbs — bones, muscles, nerves and all — within weeks. It can also repair spinal cord and retinal tissue, and is easy to breed, making it a popular biological model since 1864. But the size of its genome, and the number of repetitive sequences within it, has made full genetic analysis impossible — until now.
In a recent Nature paper, The axolotl genome and the evolution of key tissue formation regulators, lead authors Elly Tanaka of the Research Institute of Molecular Pathology in Vienna, Michael Hiller and Gene Myers, of the Max Planck Institute of Molecular Cell Biology and Genetics, and Siegfried Schloissnig of the Heidelberg Institute for Theoretical Studies, describe how they sequenced, assembled, annotated, and analyzed the complete Ambystoma mexicanum genome using PacBio long-read sequencing, optical mapping and a new genome assembler called MARVEL.
The long reads allowed the team to overcome several assembly challenges and to isolate genes unique to axolotl. They identified one crucial developmental gene in particular that was missing (PAX3); its functions were taken over by another gene (PAX7).
“Together with methods such as CRISPR-mediated gene editing, viral expression methods, transplantation and transgenesis, the axolotl is a powerful system for studying questions such as the evolutionary basis of its remarkable regeneration ability,” they conclude.
The MARVEL algorithm developed by the team was also used by Myers and his team as they sequenced and analyzed another non-traditional model organism used in labs to study everything from regeneration, stem cell biology, and aging to the evolution of parasitism: the planarian flatworm Schmidtea mediterranea.
The long-range contiguous assembly is the first of its kind among non-parasitic flatworm species, Myers et al state in their related Nature study, The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms, Previous assemblies of S. mediterranea were very fragmented, they add.
Among the discoveries they made when studying the more comprehensive genome was the worm’s ability to pause mitotic cell division in response to spindle damage, despite missing components of spindle assembly checkpoint (SAC) pathways.
“[This] suggests that our genetic and mechanistic understanding of SAC function is incomplete,” the authors write.
As suggested in a related News and Views feature by Yale University researchers Grant Parker Flowers and Craig Crews: “The new genome assemblies, when combined with the sudden ease of genetic manipulation using new genome-editing tools, will make it possible to do experiments that were previously unimaginable in model organisms such as planarians and salamanders.”
